Menopausia quirúrgica en pacientes con mutación BRCA, el papel de la terapia hormonal / Surgical Menopause in Patients with BRCA Mutation, the Role of Hormone Therapy

Introducción: las mujeres con mutación BRCA1/2 (mBRCA) tienen un riesgo aumentado de desarrollar cáncer de mama (CM) y ovario (CO). La salpingo-oforectomía bilateral (SOB) se asocia con la reducción del riesgo del 80% para CO y un 50% para CM. Se recomienda realizarla entre los 35 y 40 años. Como consecuencia se produce una menopausia prematura, con un impacto negativo sobre la calidad de vida por la presencia de síntomas climatéricos, aumento del riesgo de enfermedad cardiovascular, osteoporosis y riesgo de alteración cognitiva. La terapia hormonal (THM) es el tratamiento más eficaz para la prevención de estos síntomas. Estado del arte: distintos estudios han demostrado un mayor riesgo de CM en mujeres posmenopáusicas que reciben THM en particular con terapia combinada, estrógeno + progesterona (E+P). Según el metanálisis de Marchetti y cols., en las mujeres portadoras de mBRCA que recibieron THM, no hubo diferencias en el riesgo de CM comparando E solo con E+P. En el estudio de Kotsopoulos, incluso se encontró un posible efecto protector en aquellas que usaron E solo. Otro estudio en portadoras sanas demostró que, en las mujeres menores de 45 años al momento de la SOB, la THM no afectó las tasas de CM. Sin embargo, en las mujeres mayores de 45 años, las tasas de CM fueron más altas. Como el esquema de E+P se asocia con un mayor riesgo relativo (RR) de CM, las dosis de progestágenos utilizados se deberían limitar, eligiendo derivados naturales de progesterona, de uso intermitente para disminuir la exposición sistémica. Según diferentes guías internacionales, a las portadoras de mBRCA sanas que se someten a una SOB se les debe ofrecer THM hasta la edad promedio de la menopausia. Conclusión: la menopausia prematura disminuye la expectativa de vida; es por ello que una de las herramientas para mejorar y prevenir el deterioro de la calidad de vida es la THM. El uso de THM a corto plazo parece seguro para las mujeres portadoras de mBRCA que se someten a una SOB antes de los 45 años, al no contrarrestar la reducción del riesgo de CM obtenida gracias a la cirugía. (AU)

Introduction: women with BRCA1/2 (mBRCA) mutation have an increased risk of developing breast (BC) and ovarian (OC) cancer. Bilateral salpingo-oophorectomy (BSO) is associated with an 80% risk reduction for OC and 50% for BC. The recommended age for this procedure is 35 to 40 years. The consequence is premature menopause, which hurts the quality of life due to the presence of climacteric symptoms, increased risk of cardiovascular disease, osteoporosis, and a higher risk of cognitive impairment. Hormone therapy (MHT) is the most effective treatment for preventing these symptoms. State of the art: different studies have shown an increased risk of BC in postmenopausal women receiving MHT, particularly with combined therapy, estrogen + progesterone (E+P). According to the meta-analysis by Marchetti et al., in women carrying mBRCA who received MHT, there was no difference in the risk of BC compared to E alone with E+P. In the Kostopoulos study, there was also a possible protective effect in those who used E alone. Another study in healthy carriers showed that in women younger than 45 years at the time of BSO, MHT did not affect BC rates. However, in women older than 45 years, BC rates were higher. As the E+P scheme is associated with a higher RR of BC, the doses of progestogens should be limited, choosing natural progesterone byproducts of intermittent use to decrease systemic exposure. According to various international guidelines, healthy mBRCA carriers undergoing BSO should be offered MHT until the average age of menopause. Conclusion: premature menopause decreases life expectancy, which is why one of the tools to improve and prevent deterioration of quality of life is MHT. Short-term use of MHT appears safe for women with mBRCA who undergo BSO before age 45 as it does not counteract the reduction in the risk of MC obtained by surgery. (AU)

Clinical features and management of women with borderline ovarian tumors in a single center in Brazil / Características clínicas e manejo de mulheres com tumores borderline de ovário em um hospital no Brasil

Abstract Objective The aim of the present study was to describe and analyze data of 57 women with borderline ovarian tumors (BOTs) regarding histological characteristics, clinical features and treatment management at the Department of Obstetrics and Gynecology of the Universidade Estadual de Campinas (Unicamp, in the Portuguese acronym). Methods The present retrospective study analyzed data obtained from clinical and histopathological reports of women with BOTs treated in a single cancer center between 2010 and 2018. Results A total of 57 women were included, with a mean age of 48.42 years old (15.43- 80.77), of which 30 (52.63%) were postmenopausal, and 18 (31.58%) were < 40 years old. All of the women underwent surgery. A total of 37 women (64.91%) were submitted to complete surgical staging for BOT, and none (0/57) were submitted to pelvic or paraortic lymphadenectomy. Chemotherapy was administered for two patients who recurred. The final histological diagnoses were: serous in 20 (35.09%) cases, mucinous in 26 (45.61%), seromucinous in 10 (17.54%), and endometrioid in 1 (1.75%) case. Intraoperative analyses of frozen sections were obtained in 42 (73.68%) women, of which 28 (66.67%) matched with the final diagnosis. The mean follow-up was of 42.79 months (range: 2.03-104.87 months). Regard ingthe current status of the women, 45(78.95%) are alive without disease, 2(3.51%) arealive with disease, 9 (15.79%) had their last follow-up visit > 1 year beforethe performanceof the present study but arealive, and 1 patient(1.75%) died of another cause. Conclusion Women in the present study were treated according to the current guidelines and only two patients recurred.

Resumo Objetivo O objetivo do presente estudo foi descrever uma série de 57 mulheres com tumores borderline de ovário (TBO) em relação às características histológicas, clínicas, e ao manejo do tratamento realizado no Departamento de Obstetrícia e Ginecologia da Universidade Estadual de Campinas (Unicamp). Métodos O presente estudo retrospectivo analisou dados obtidos dos registros clínicos e histopatológicos de mulheres com TBO tratadas em um único centro oncológico de 2010 a 2018. Resultados Um total de 57 mulheres foram incluídas, com uma média de idade de 48,42 anos (15,43-80,77), das quais 30 (52,63%) eram menopausadas, e 18 (31,58%) tinham < 40 anos. Todas as mulheres foram operadas. Um total de 37 mulheres (64,91%) foram submetidas a cirurgia de estadiamento completo para TBO, e nenhuma foi submetida a linfadenectomia pélvica ou paraórtica. O tratamento com quimioterapia foi administrado em duas pacientes que recidivaram. Os diagnósticos histológicos finais foram: seroso em 20 mulheres (35,09%), mucinoso em 26 (45,61%), seromucinoso em 10 (17,54%) e endometrióide em 1 (1,75%). A avaliação histológica intraoperatória foi realizada em 42 (73,68%) das mulheres, das quais 28 (66,67%) foram compatíveis com os diagnósticos finais. O tempo médio de seguimento foi de 42,79 meses (variando de 2,03 a 104,87 meses). Em relação ao status atual das mulheres, 45 (78.95%) estão vivas sem doença, 2 (3,51%) estão vivas com doença, 9 (15.79%) tiveram a última consulta de seguimento há > 1 ano antes da realização do presente estudo, mas estão vivas, e 1 paciente faleceu por outra causa. Conclusão As mulheres do presente estudo foram tratadas de acordo com as recomendações atuais e apenas duas mulheres apresentaram recorrência.